CAMELIA REGISTRY Slovakia and Czech Republic

CAMELIA REGISTRY Slovakia and Czech Republic Indrák K. 1,Faber E. 1,Demečková E. 2, Demitrovičová L. 3, Voglová J. 4, Jindra P. 5, Markuljak I. 6, Chudej J. 7, Cmunt E. 8, Tóthová E. 9, Štecová N. 10, Palášthy S. 11, Mužík J. 12, Dušek L. 12 1. Dept. Hematooncology Olomouc, CR 2. Dept. Hematology and Blood Transfusion, Bratislava, SR 3. Dept. Internal Medicine, Division Hematol. and Blood Transfusion, NCI, Bratislava, SR 4. 4th Dept. Internal Medicine - Hematology, Hradec Králové, CR 5. Dept. Hematooncology, Plzeň, CR 6. Dept. Hematology and Blood Transfusion, Martin, SR 7. Dept. Hematology, Banská Bystrica, SR 8. Dept. Internal Medicine, General University Hospital, Prague, CR 9. Dept. Hematology and Hematooncology, Košice, SR 10. HEMKO Ltd., Hematology and Onco-Hematology Outpatient Dept., Košice, SR 11. J. A. Rieman Health Centre, Dept. Hematology, Prešov, SR 12. Institute of Biostatistics and Analyses, Brno, CR Institute of Biostatistics and Analyses Masaryk University

Characteristics of CML patients CAMELIA CZ and SK registry in period 2000-2012 Total N = 1264 patients 120 retrospective prospective Number of patients 100 80 60 40 20 0 20 19 20 12 12 18 4 2 9 11 3 2 1 7 6 13 9 12 <=1990 1991 1992 1993 1994 1995 1996 1997 1998 10 27 15 20 19 54 39 58 1999 2000 2001 2002 2003 20 6 67 73 6 86 Year of CML diagnosis 6 7 11 4 67 75 79 71 5 99 2004 2005 2006 2007 2008 2009 2010 2011 4 14 69 73 TKI treatment no TKI (any time) treatment Total N = 994 N = 270 N = 1264 Chronic phase 922 (92.8%) 236 (87.4%) 1158 (91.6%) Accelerated phase 51 (5.1%) 24 (8.9%) 75 (5.9%) Blast crisis 21 (2.1%) 10 (3.7%) 31 (2.5%) 2012 no TKI treatment N = 270 TKI treatment (any time) N = 994

Population distribution of the CML patients followed in the Czech CAMELIA Registry 4 2 CAMELIA Registry population coverage: 5.6 million inhabitants INFINITY Registry 5 million inhabitants 3 1 Patients registered in CAMELIA database in period 2000 2012 N = 646 (TKI 518) 1. Olomouc 2. Hradec Králové 3. Plzeň 4. VFN Praha N = 211 (TKI 189) N = 203 (TKI 160) N = 186 (TKI 137) N = 46 (TKI 32)

5.4 million inhabitants The population distribution of the CML patients followed in the Slovak CAMELIA Registry CAMELIA Registry 3 7 2 4 6 5 1 Patients registered in CAMELIA database in period 2000 2012 N = 626 (TKI 476) 1. Bratislava Hematol. N = 256 (TKI 178) 2. NCI Bratislava N = 94 (TKI 93) 3. Martin N = 87 (TKI 59) 4. Bánská Bystrica N = 78 (TKI 49) 5. HEMKO Ltd. Košice N = 66 (TKI 66) 6. Košice N = 37 (TKI 31) 7. Prešov * N = 8 data collection in process

Characteristic of CML patients treated with TKI and enroled in CAMELIA CZ and CAMELIA SK registry in period 2000-2012 Total N = 994 patients Sex Age at diagnosis Male Female Total 45% N = 545 N = 449 N = 994 Mean 51 y 52 y 51 y Median 53 y 53 y 53 y Min - max 17-86 y 17-89 y 17-89 y 55% 20 % 15 Male (N = 545) 10 Female (N = 449) 5 0 <20 20-24 25-29 30-34 35-39 40-44 45-49 50-54 Age (years) 55-59 60-64 65-69 70-74 75-79 80-84 85+

Start of TKI treatment of 994 CML patients in time - INCIDENCE Number of patients 120 100 80 60 40 20 0 Imatinib 2 nd line Imatinib 1 st line Dasatinib Nilotinib TKI in total 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 Year of start of treatment

TKI treatment of 994 CML patients in time - PREVALENCE Number of patients 900 800 700 600 500 400 300 200 100 0 Imatinib 2 nd line Imatinib 1 st line Dasatinib Nilotinib TKI in total 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 Year of treatment

Time on TKI treatment of 994 CML patients in period 2000-2012 1.0 0.9 Proportion of patients on treatment 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 Log-rank test p = 0.019 TKI in total (N = 994) TKI in 1 st line (N = 710) TKI in 2 nd line (N = 284) 0.0 0 12 24 36 48 60 72 84 96 108 120 132 Time from start of TKI treatment (months)

OS of 994 CML patients on TKI treatment in period 2000 2012 1.0 0.9 Proportion of surviving patients 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 Log-rank test p < 0.001 TKI in total (N = 994) TKI in 1 st line (N = 710) TKI in 2 nd line (N = 284) 0.0 0 12 24 36 48 60 72 84 96 108 120 132 Time from start of TKI treatment (months)

PFS of CP CML patients on TKI treatment in 1 st line according to risk scores Proportion of patients without progression 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 Sokal score low risk (N = 252) intermediate risk (N = 238) high risk (N = 152) Log-rank test p 0.088 0.022 <0.001 0 12 24 36 48 60 72 84 96 108 120 132 Proportion of patients without progression 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 Hasford score low risk (N = 269) intermediate risk (N = 293) high risk (N = 80) Log-rank test p 0.038 0.001 <0.001 0 12 24 36 48 60 72 84 96 108 120 132 Time from start of TKI treatment (months) Time from start of TKI treatment (months) Proportion of patients without progression 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 low risk (N = 550) high risk (N = 92) EUTOS score Log-rank test p 0.160 0.0 0 12 24 36 48 60 72 84 96 108 120 132 Time from start of TKI treatment (months)

OS of CP CML patients on TKI treatment in 1 st line according to risk scores 1.0 Sokal score 1.0 Hasford score 0.9 0.9 Proportion of surviving patients 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 low risk (N = 252) intermediate risk (N = 238) high risk (N = 152) Log-rank test p 0.070 0.295 0.007 Proportion of surviving patients 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 low risk (N = 269) intermediate risk (N = 293) high risk (N = 80) Log-rank test p 0.001 0.090 <0.001 0.0 0 12 24 36 48 60 72 84 96 108 120 132 0.0 0 12 24 36 48 60 72 84 96 108 120 132 Time from start of TKI treatment (months) Time from start of TKI treatment (months) 1.0 EUTOS score 0.9 Proportion of surviving patients 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 low risk (N = 550) high risk (N = 92) Log-rank test p 0.373 0.0 0 12 24 36 48 60 72 84 96 108 120 132 Time from start of TKI treatment (months)

CAMELIA publications 2010-2011 1. FABER E., INDRÁK K. ET AL. Chronická myeloidní leukemie. Galén 2010 2. E. FABER, D. FRIEDECKÝ, K. MIČOVÁ ET AL. Imatinib dose escalation in two patients with chronic myeloid leukemia, with low trough imatinib plasma levels measured at various intervals from the beginning of therapy and with suboptimal treatment response, leads to the achievement of higher plas. IJH, 2010, 91(5): 897-902. 3. P. ROHOŇ, Š. ROŽMANOVÁ, J. ZAPLETALOVÁ ET AL. Výsledky liečby pacientov v chronickém fáze chronickej myelocytovej leukémie na HOK v Olomouci v rokoch 2000-2009: prognostický význam Sokalovho indexu a ELN kritérií. Transfuze a hematologie dnes, 2010, 16(4): 202-209. 4. P. ROHON, M. DIVOKA, L. CALABKOVA et al. Identification of e6a2 bcr-abl fusion in Philadephia positive CML with marked basofilia: implication for treatment strategy. Biomed Pap 2011,155: 187-90. 5. E. FABER, J. MUŽÍK, V. KOZA ET AL. Treatment of consecutive patients with chronic myeloid leukemia in the cooperating centres form the Czech Republic and the whole of Slovakia after 2000 a report from the population-based CAMELIA Registry. EJH 2011, 87(2):157-168. 6. VOGLOVÁ J, MUŽÍK J, FABER E, ET AL. Incidence of second malignancies during treatment of chronic myeloid leukemia with tyrosine kinase inhibitors in the Czech Republic and Slovakia. Neoplasma. 2011; 58 (3): 256-262.

CAMELIA publications 2012-2013 1. E. Faber, D. Friedecky, K. Micova, et al.: Imatinib trough plasma levels do not correlate with the response to therapy in patients with chronic myeloid leukemia in routine clinical setting. An Hematol. 01/2012; DOI:10.1007/s00277-011-1394-2. E. Faber, A. Kuba, J. Zapletalova, et al. on Behalf of Cooperating Group: Operational Cures After Interferon-Alpha in Patients with Chronic Myeloid Leukemia in Central and Northern Moravia. JOURNAL OF INTERFERON & CYTOKINE RESEARCH, 32, 5, 2012 Ş Mary Ann Liebert, 3. Š. Rožmanová, P. Rohoň, M. Divoká, et al.: Hodnocení časné molekulární odpovědi po 3 měsících léčby imatinibem může u nemocných s chronickou myeloidní leukemií přispět kupřesnění odhadu prognózy zkušenosti jednoho centra. Transf. Hematol. dnes 18, 2012, 66-71 4. E. Faber, D. Friedecky, K. Micova, et al.: Imatinib dose escalation in two patients with chronic myeloid leukemia, with low trough imatinib plasma levels measured at various intervals from the beginning of therapy and with suboptimal treatment response, leads to the achievement of higher plasma levels and major molecular response. IJH 04/2012; 91(5):897-902. 5. E. Faber, A. Kuba, J. Zapletalova, et al.: Interferon-alpha in chronic myeloid leukemia revisited: A long-term retrospective study in Central and Northern Moravia. Biomed Pap 2012;

CAMELIA joint publications 2010-2013 1. H. Klamova, E. Faber, D. Zackova et al.: Dasatinib in imatinib-resistant or intolerant CML patients: data from the clinical practise of 6 hematological centers in the Czech Republic. Neoplasma 57 (4) 355 359, 2010 2. A. Kreutzman, P. Rohon, E. Faber, K. Indrak et al.: Chronic myeloid leukemia patients in prolonged remission following interferon-α monotherapy have distinct cytokine and oligoclonal lymphocyte profile. PLoS ONE 01/2011; 6(8):e23022. DOI:10.1371/journal.pone.0023022 3. H. Klamová 1, K. Machová Poláková 1, J. Mužík 2, et al.: Evaluation of 5-year imatinib treatment of 458 patients with CP-CML in routine clinical practice and prognostic impact of different BCR-ABL cutoff levels. Cancer Medicine 2, 2, 216-225, 4, 2013 4. T. Pavlik, E. Janousova, J. Mayer, K. Indrak, et al: Current survival measures reliably reflect modern sequential treatment in CML: correlation with prognostic stratifications. AJH. 2013 doi: 10.1002/ajh.23508, 6/2013

CAMELIA participation on ELN WP4 clinical projects and the proposed projects 1. EUTOS for CML out-study patients accepted 240 patients 2. EUTOS for CML population-based registry reported in total 312 patients from region of 11 mil population diagnosed in between 7/2009-12/2012, it means incidence of 0.81/100,000 per year 3. EURO-SKI individual participation of the Czech republic CAMELIA centre (Olomouc, Hradec Kralove and Pilzen) through Infinity Registry 4. Pregnancy study interest in participation of CAMELIA SR (Responsible Z. Sninska, MD, PhD.) and CR (Responsible K. Steinerova, MD, PhD.) The proposed CAMELIA projects: 5. The prognostic significance of anemia for CML (Prof. E. Faber, MD, PhD.) 6. The validation of prognostic risk score in CML patients in real clinical practice (Z. Sninska, MD, PhD.) 7. The impact of cytogenetic abnormalities on treatment results of CML patients (Prof. M. Jarosova, MA, PhD., T. Pavlik, MA, PhD.) 8. The analyses of nilotinib treatment in clinical practice (Prof. E. Tóthová, MD, PhD.)

Camelia group participants Olomouc 4.5.2011 Brno 4/2009 Thank you for your attention!